(Section 1, Chapter 2, Part 3) Neuroscience Online: An Electronic Textbook for the Neurosciences | Department of Neurobiology and Anatomy - The University of Texas Medical School at Houston

Pumps and Leaks

It is easy to receive the impression that there is a "gush" of Na⁺ that comes into the cell with each action potential. Although, there is some influx of Na⁺, it is minute compared to the intracellular concentration of Na⁺. The influx is insufficient to make any noticeable change in the intracellular concentration of Na⁺. Therefore, the Na⁺ equilibrium potential does not change during or after an action potential. For any individual action potential, the amount of Na⁺ that comes into the cell and the amount of K⁺ that leaves are insignificant and have no effect on the bulk concentrations. However, without some compensatory mechanism, over the long-term (many spikes), Na⁺ influx and K⁺ efflux would begin to alter the concentrations and the resultant Na⁺ and K⁺ equilibrium potentials. The Na⁺-K⁺ pumps in nerve cells provide for the long-term maintenance of these concentration gradients. They keep the intracellular concentrations of K⁺ high and the Na⁺ low, and thereby maintain the Na⁺ equilibrium potential and the K⁺ equilibrium potential. The pumps are necessary for the long-term maintenance of the "batteries" so that resting potentials and action potentials can be supported.

Test Your Knowledge

Question 1
A
B
C
D
E

Drug X, when applied to a nerve axon, results in both a gradual decrease in the amplitude of individual action potentials and a depolarization of the resting potential, both of which develop over a period of several hours. The drug is most likely:

A. Blocking the voltage-dependent Na⁺ permeability

B. Blocking the voltage-dependent K⁺ permeability

C. Blocking the (Na⁺ -K⁺) pump

D. Blocking the process of Na⁺ inactivation

E. Increasing the rate at which voltage-dependent changes in K⁺ permeability occur

A. Blocking the voltage-dependent Na⁺ permeability This answer is INCORRECT.

Blocking the voltage-dependent sodium permeability would decrease the amplitude of the action potential, but it would probably do nothing to the resting potential. If it did anything to the resting potential, it would lead to a hyperpolarization, not a depolarization as is the case with drug X.

B. Blocking the voltage-dependent K⁺ permeability

C. Blocking the (Na⁺ -K⁺) pump

D. Blocking the process of Na⁺ inactivation

E. Increasing the rate at which voltage-dependent changes in K⁺ permeability occur

A. Blocking the voltage-dependent Na⁺ permeability

B. Blocking the voltage-dependent K⁺ permeability This answer is INCORRECT.

The voltage-dependent potassium channels are generally not activated unless the membrane potential is fairly depolarized. Thus, blocking the voltage-dependent potassium permeability would have very little, if any, effect on the resting potential. Also, blocking the voltage-dependent potassium permeability would have a tendency to perhaps increase the amplitude (and duration) of the action potential rather than decreasing it.

C. Blocking the (Na⁺ -K⁺) pump

D. Blocking the process of Na⁺ inactivation

E. Increasing the rate at which voltage-dependent changes in K⁺ permeability occur

A. Blocking the voltage-dependent Na⁺ permeability

B. Blocking the voltage-dependent K⁺ permeability

C. Blocking the (Na⁺ -K⁺) pump This answer is CORRECT!

Blocking the sodium potassium pump leads to a gradual influx of sodium into the cell, and efflux of potassium out of the cell. These changes in concentration lead to a change in the equilibrium potential for potassium, as well as for sodium. As the equilibrium potential for potassium becomes more positive, the resting potential becomes more positive (i.e., more depolarized). Because of the sodium influx into the cell, the equilibrium potential for sodium is changed, namely, it is less positive. And because the peak amplitude of the action potential is dependent upon the value of the sodium equilibrium potential, the peak amplitude of the action potential would also decrease over time.

D. Blocking the process of Na⁺ inactivation

E. Increasing the rate at which voltage-dependent changes in K⁺ permeability occur

A. Blocking the voltage-dependent Na⁺ permeability

B. Blocking the voltage-dependent K⁺ permeability

C. Blocking the (Na⁺ -K⁺) pump

D. Blocking the process of Na⁺ inactivation This answer is INCORRECT.

Blocking the process of sodium inactivation would affect primarily the repolarization phase of the action potential. There would be no change in the resting potential. The only consequence would be that the action potential would have a greater duration than normal.

E. Increasing the rate at which voltage-dependent changes in K⁺ permeability occur

A. Blocking the voltage-dependent Na⁺ permeability

B. Blocking the voltage-dependent K⁺ permeability

C. Blocking the (Na⁺ -K⁺) pump

D. Blocking the process of Na⁺ inactivation

E. Increasing the rate at which voltage-dependent changes in K⁺ permeability occur This answer is INCORRECT.

Increasing the rate in which voltage-dependent changes in potassium permeability occur would only affect the duration of the action potential. Perhaps if there was an increase in the rate, there might also be a slight decrease in the amplitude of the action potential, but there would be no change in the resting potential.

Types of Membrane Channels

So far, two basic classes of channels, voltage-dependent or voltage-gated channels and voltage independent channels, have been considered. Voltage-dependent channels can be further divided based on their permeation properties into voltage-dependent Na⁺ channels and voltage-dependent K⁺ channels. There are also voltage-dependent Ca²⁺ channels (see below). Indeed, there are multiple types of Ca²⁺ channels and about 20 different types of voltage-dependent K⁺ channels. Nevertheless, all these channels are conceptually similar. They are membrane channels that are normally closed and as a result of changes in potential, the channel (pore) is opened. The amino acid sequence of these channels is known in considerable detail and specific amino acid sequences have been related to specific aspects of channel function (e.g., ion selectivity, voltage gating, inactivation). A third major channel class, the transmitter-gated or ligand-gated channels, will be described later.

Absolute and Relative Refractory Periods

The absolute refractory period is a period of time after the initiation of one action potential when it is impossible to initiate a second action potential no matter how much the cell is depolarized. The relative refractory period is a period after one action potential is initiated when it is possible to initiate a second action potential, but only with a greater depolarization than was necessary to initiate the first. The relative refractory period can be understood at least in part by the hyperpolarizing afterpotential. Assume that an initial stimulus depolarized a cell from -60 mV to -45 mV in order to reach threshold and then consider delivering the same 15-mV stimulus sometime during the after-hyperpolarization. The stimulus would again depolarize the cell but the depolarization would be below threshold and insufficient to trigger an action potential. If the stimulus was made larger, however, such that it again was capable of depolarizing the cell to threshold (-45 mV), an action potential could be initiated.

The absolute refractory period can be explained by the dynamics of the process of Na⁺-inactivation, the features of which are illustrated in Figure 2.10. Here, two voltage clamp pulses are delivered. The first pulse produces a voltage-dependent increase in the Na⁺ permeability which then undergoes the process of inactivation. If the two pulses are separated sufficiently in time, the second pulse produces a change in the Na⁺ conductance, which is identical to the first pulse. However, if the second pulse comes soon after the first pulse, then the change in Na⁺ conductance produced by the second pulse is less than that produced by the first. Indeed, if the second pulse occurs immediately after the first pulse, the second pulse produces no change in the Na⁺ conductance. Therefore, when the Na⁺ channels open and spontaneously inactivate, it takes time (several msec) for them to recover from that inactivation. This process of recovery from inactivation underlies the absolute refractory period. During an action potential the Na⁺ channels open and then they become inactivated. Therefore, if a second stimulus is delivered soon after the one that initiated the first spike, there will be few Na⁺ channels available to be opened by the second stimulus because they have been inactivated by the first action potential.

Figure 2.10

Action Potential Laboratory

Click here to go to the interactive Action Potential Laboratory to examine the ways in which the action potential is effected by changes in the Na⁺ conductance, K⁺ conductance and equilibrium potentials for Na⁺ and K⁺.

Action Potential Laboratory

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